ABSTRACT

Production of oxygen radicals in biological systems may be tentatively divided into four categories: nonenzymatic production during the oxidation of natural substrates; enzymatic production catalyzed by reductases, dehydrogenases, and other enzymes; the drug and xenobiotic stimulation of superoxide formation; and the production of oxygen radicals by whole cells. The search for the "physiological" metal ion catalyst of the Fenton reaction becomes one of the key questions in studying hydroxyl radical production. The presence of iron ions or complexes is an obligatory condition for the production of active oxygen species by xanthine oxidase. Formation of the superoxide ion in mitochondria was first shown by G. Loschen et al., who found that washed mitochondrial membranes from beef heart mitochondria oxidized epinephrine in the presence of antimycin A. SOD inhibited epinephrine oxidation. H. J. Forman and J. Kennedy concluded that primary mitochondrial dehydrogenases rather than electron carriers are real generators of the superoxide ion.